Studies of human patients with brain damage have indicated that neural structures of the limbic system are mediators of the processes of learning and memory. The proposed studies are designed to contribute to an understanding of the basic mechanisms of learning, memory, and pathology of memory by studying the acquisition of discriminative unit activity in limbic structures, which accompanies discrimination learning and reversal in intact behaving animals. Past studies have suggested that the cingulate cortex, the anteroventral (AV) thalamus and the hippocampal formation are brain sites which function interactively to perform encoding and extraction of the significance of cues (e.g., conditional stimuli) in discriminative learning situations. The code for significance is critical for the ability to predicate behavior on cue-occurrence. In addition, studies have indicated that the deep laminae of cingulate cortex are the sites of the initialmost encoding at the outset of training. However with continuing training the code for significance is relegated to neurons of the AV thalamus, by virtue of repeated discriminative neuronal inputs to the AV thalamus from the deep laminae. Once relegation of the code to thalamus has occurred, the operation of the code for continuing task performance, and any recoding that is called for (e.g., reversal), are carried out at the level of the AV thalamus. Inputs to the AV thalamus from the hippocampal formation (subiculum) are essential in bringing about relegation of the code to that structure, and reformulation of the AV thalamic code, as in reversal. The major objectives of the proposed research involve five experiments designed to test specific predictions from the model. Each experiment involves neuronal recording during discriminative acquisition, retention and reversal, in conjunction with focalized brain damage induced either before training or after training but prior to reversal. In each case a specific prediction about neuronal activity, and about behavior, will be tested. The results are expected to lead to refinement of the model, and ultimately to shed light on the detailed cortical, thalamic and hippocampal mechanisms that are involved in mediating discriminative learning and performance.